Carrion's disease

Oroya fever or Carrion's disease is an infectious disease produced by Bartonella bacilliformis infection.

It is named after Daniel Alcides Carrión.^[1]

History

Huaco from Ancash

Carrion's disease has been known since Pre-Inca times. Numerous artistic representations in clay (called "huacos") of the chronic phase have been found in endemic areas. The Spanish chronist, Garcilaso De La Vega described a disease with warts in Spanish troops during the conquest of Inca Empire, in Coaque-Ecuador. For a long time it was thought that the disease was endemic only in Peru and that it had only one phase, the "Peruvian wart" or "verruga peruana"^[2]

In 1875 an outbreak, characterized by fever and anemia occurred in the region of construction of the railroad line between Lima and La Oroya.^[3] This is the source of the name "oroya fever" sometimes used to describe acute bartonellosis.^[4]

In August 1885, Daniel Alcides Carrión, a Peruvian medical student, attempted to inoculate himself with material taken from a verruga lesion of a chronic patient (Carmen Paredes), with the help of a local physician (Evaristo Chavez). After 3 weeks he developed classic symptoms of the acute phase of the disease, thus establishing a common etiology (cause) for these two diseases.^[5] He died from bartonellosis on October 5, 1885 and was recognized as a martyr of Peruvian medicine and the term Carrión's Disease is still used today (Peruvian Medicine Day is October 5 in honor to him).

Alberto Barton, a Peruvian microbiologist, identified Bartonella bacilliformis within erythrocytes in 1905, and announced the discovery of the etiologic agent (Barton bacillus) in 1909, which was called Bartonella bacilliformis.

Etiologic agent

Carrion's disease is caused by Bartonella bacilliformis.^[6][7] Recent investigations show that Candidatus Bartonella ancashi may cause verruga peruana, although it may not meet all of Koch's postulates. There has been no experimental reproduction of the Peruvian wart in animals and there is little research on the disease's natural spread or impact in native animals.

Epidemiology

Sand flies serve as vectors for B. bacilliformis.^[6] Carrion's disease is found only in Peru, Ecuador, and Colombia.^[8] It is endemic, or consistently present, in some areas of Peru, where most cases are reported,^[6] and is caused by infection with the bacterium Bartonella bacilliformis and transmitted by sandflies of genus Lutzomyia.^[9] Children have historically been among the most commonly affected by Carrion's disease. Mortality in the last 50 years of study have ranged from 10-23%, and some studies show that the disease disproportionately affected children and pregnant women;^[10] however, mortality is often due to comorbid infections and indirect complications of the respiratory, cardiovascular, neurological, or gastrointestinal systems.^[10]

As of December 2015, there is no knowledge of any other vectors or nonhuman reservoirs of the disease.^[6]

It is believed that outbreaks of Carrion's disease are influenced to the El Nino Southern Oscillation climate phenomena.^[11][12][13]

There are few methods of preventing Carrion's disease, due to the prevalence of the sand flies that spread the disease in its range.^[6] Suggestions for preventing Carrion's generally focuses on minimizing the risk of contact with its vector, the sand flies. This includes the use of insect repellents, protective clothing, and avoiding the habitat at risk during times of sand fly activity.^[6] It has been suggested that milder cases of Carrion's disease often go undiagnosed and unrecognized, and so epidemiological numbers may be low.^[10] Infection by Bartonella is not always accompanied by physical symptoms of Carrion's disease.^[10]

Clinical signs and symptoms

The clinical symptoms of bartonellosis are pleomorphic and some patients from endemic areas may be asymptomatic. The two classical clinical presentations are the acute phase and the chronic phase, corresponding to the two different host cell types invaded by the bacterium (red blood cells and endothelial cells). An individual can be affected by either or both phases.^[11][14]

Acute phase: (Carrion's disease or Oroya Fever^[6]) also called the hematic phase,^[11] the most common findings are fever (usually sustained, but with temperature no greater than 102 °F (39 °C)), pallor, malaise, nonpainful hepatomegaly, jaundice, lymphadenopathy, and splenomegaly. This phase is characterized by severe hemolytic anemia and transient immunosuppression. The case fatality ratios of untreated patients exceeded 40% but reach around 90% when opportunistic infection with Salmonella spp occurs. In a recent study the attack rate was 13.8% (123 cases) and the case-fatality rate was 0.7%.

Other symptoms include headache, muscle aches, and general abdominal pain.^[6] Some studies have suggested a link between Carrion's disease and cardiac murmurs due to the disease's impact on the circulatory system. In children, symptoms of anorexia, nausea, and vomiting have been investigated as possible symptoms of the disease.^[11]

Most of the mortality of Carrion's disease occurs during the acute phase. Studies vary in their estimates of mortality. In one study, mortality has been estimated as low as just 1% in studies of hospitalized patients, to as high as 88% in untreated, unhospitalized patients.^[11] In developed countries, where the disease rarely occurs, it is recommended to seek the advice of a specialist in infectious disease when diagnosed.^[10] Mortality is often thought to be due to subsequent infections due to the weakened immune symptoms and opportunistic pathogen invasion, or consequences of malnutrition due to weight loss in children.^[8][11] In a study focusing on pediatric and gestational affects of the disease, mortality rates for pregnant women with the acute phase were been estimated at 40% and rates of spontaneous abortion in another 40%.^[11]

chronic phase

Chronic phase: (Verruga Peruana or Peruvian Wart) also called the eruptive phase or tissue phase, in which the patients develop a cutaneus rash produced by a proliferation of endothelial cells and is known as "Peruvian warts" or "verruga peruana". Depending of the size and characteristics of the lesions, there are three types: miliary (1–4 mm), nodular or subdermic and mular (>5mm). Miliary lesions are the most common. The lesions often ulcerate and bleed.^[6]

The most common findings are bleeding of verrugas, fever, malaise, arthralgias (joint pain), anorexia, myalgias, pallor, lymphadeopathy, and hepato-splenomegaly.

On microscopic examination, the chronic phase and its rash is produced by angioblastic hyperplasia, or the increased rates and volume of cell growth in the tissues that form blood vessels. This results in a loss of contact between cells and a loss of normal functioning.^[7][11]

The chronic phase is the more common phase. Mortality during the chronic phase is very low.^[6][11]

Diagnosis

thin blood film

Diagnosis during the acute phase can be made by obtaining a peripheral blood smear with Giemsa stain, Columbia-blood agar cultures, immunoblot, IFI, and PCR. Diagnosis during the chronic phase can be made using a Warthin-Starry stain of wart biopsy, PCR, and immunoblot.

Treatment

Because Carrion's disease is often comorbid with Salmonella infections, Chloramphenicol has historically been the treatment of choice.^[10]

The drug of choice during the acute phase is Quinolones (such as ciprofloxacin)^[10] or Chloramphenicol in adults and Chloramphenicol plus beta lactams in children. Chloramphenicol-resistant B. bacilliformis has been observed.^[10][11]

During the eruptive phase, in which chloramphenicol is not useful, azithromycin, erythromycin, and ciprofloxacin have been used successfully for treatment. Rifampin or macrolides are also used to treat both adults and children.^[10][11]

Because of the high rates of comorbid infections and conditions, multiple treatments are often required. These have included the use of corticosteroids for respiratory distress, red blood cell tranfusions for anemia, pericardiectomies for pericardial tamponades, and other standard treatments.^[11][13]

See also

• Verruga peruana

References

External links

• Oroya fever
• Human Bartonellosis caused by Bartonella bacilliformis